SBIR Phase II: Mass Spectrometry Imaging for High-Throughput Discovery of Enzyme Activity

SBIR 第二阶段：用于高通量发现酶活性的质谱成像

• 批准号: 1151957
• 负责人: Matthew Greving
• 金额: $ 49.92万
• 依托单位: Nextval Inc.
• 依托单位国家: 美国
• 项目类别: Standard Grant
• 财政年份: 2012
• 资助国家: 美国
• 起止时间: 2012-04-01 至 2014-09-30
• 项目状态: 已结题
• 来源: https://www.nsf.gov/awardsearch/showAward?AWD_ID=1151957&HistoricalAwards=false
• 关键词: SBIR; Phase; II; Mass; Spectrometry

This Small Business Innovation Research (SBIR) Phase II project will further develop and commercialize a groundbreaking technology for high-throughput cost-effective screening and analysis. This technology addresses the growing disparity between the ability to generate high-complexity chemical libraries with molecular genetics and combinatorial chemistry approaches, versus the ability to rapidly screen these libraries for high-value molecules. This new high-throughput screening product is a novel integration of an acoustic ejection device with chip-based mass spectrometry to produce mass readout microarrays that are analyzed in high-throughput with mass spectrometry imaging and computational algorithms. Phase II efforts will focus on a high-throughput screening product for cellulase enzyme discovery, a critical enzyme in the production of alternative fuels that is limited by optically based screens which often generate false leads. Importantly, this integrated high-throughput platform does not require sample labeling, is applicable to a broad range of chemical activities, and provides much more information from a single readout than current approaches. Phase II development will produce a commercial screening technology with these advantages and analysis throughput of 250,000 samples/week, while maintaining the flexibility for future applications in the industrial, pharmaceutical and diagnostic markets.The broader impact/commercial potential of this project are cost-effective high-throughput discovery of new enzymes and molecules with enhanced or novel activities in the industrial, environmental, pharmaceutical or diagnostic markets. Also, the proposed technology enables entirely new types of high-throughput screens that are currently inaccessible with existing technologies. Most immediately this high-throughput screening product will be commercialized for application in the $1 billion industrial enzyme market with specific focus on one of the largest fractions of this market, the enzymes important for efficient and economically viable production of second-generation alternative fuels. Beyond the application to alternative fuels, Phase II development will produce a flexible discovery platform that can be expanded to numerous commercial markets. For example, the Phase II developments can also help develop new lower-cost therapeutics by reducing false leads and enable higher specificity diagnostics and testing by providing much more chemical information.

这一小型企业创新研究(SBIR)第二阶段项目将进一步开发一项突破性技术并将其商业化，以实现高通量、高成本效益的筛选和分析。这项技术解决了用分子遗传学和组合化学方法生成高复杂性化学库的能力与快速筛选这些库中高价值分子的能力之间日益扩大的差距。这种新的高通量筛选产品是声喷射设备与基于芯片的质谱学的新型集成，以产生海量读出微阵列，并使用质谱学成像和计算算法对其进行高通量分析。第二阶段的工作将集中在用于纤维素酶发现的高通量筛选产品上，纤维素酶是生产替代燃料的关键酶，受到经常产生错误线索的光学筛查的限制。重要的是，这种集成的高通量平台不需要样品标记，适用于广泛的化学活动，并且比目前的方法从单一读数中提供更多的信息。第二阶段的开发将产生一种商业筛选技术，具有这些优势和每周25万个样本的分析吞吐量，同时保持未来在工业、制药和诊断市场应用的灵活性。该项目的更广泛影响/商业潜力是在工业、环境、制药或诊断市场以成本效益高的高通量发现具有增强或新颖活性的新酶和分子。此外，拟议的技术还使现有技术无法获得的全新类型的高通量屏幕成为可能。这种高通量筛选产品将立即商业化，应用于10亿美元的工业酶市场，重点放在该市场最大份额之一的酶上，这种酶对高效和经济可行地生产第二代替代燃料非常重要。除了替代燃料的应用，第二阶段的开发将产生一个灵活的发现平台，可以扩展到许多商业市场。例如，第二阶段的开发还可以通过减少虚假线索来帮助开发新的低成本疗法，并通过提供更多的化学信息来实现更高的特异性诊断和测试。